TABLE 4.
Treatment of an influenza A/Duck/MN/1525/81 (H5N1) wild-type (amantadine-sensitive) virus infection in mice with amantadine, oseltamivir, and ribavirin used alone or in combinationa
| Compound 1 (mg/kg/day) | Compound 2 (mg/kg/day) | No. of survivors/total no.c,d | MDD ± SDb |
|---|---|---|---|
| Amantadine (10) | 3/10 | 10.1 ± 3.2** | |
| Oseltamivir (40) | 1/10 | 8.9 ± 0.6*** | |
| Oseltamivir (20) | 3/10 | 10.0 ± 2.4*** | |
| Ribavirin (40) | 4/10* | 8.0 ± 1.3 | |
| Ribavirin (20) | 2/10 | 8.8 ± 1.3** | |
| Amantadine (10) | Oseltamivir (40) | 10/10***,φφ,ϕ | |
| Amantadine (10) | Oseltamivir (20) | 9/10***,φ | 11.0 |
| Amantadine (10) | Ribavirin (40) | 10/10***,φ | |
| Amantadine (10) | Ribavirin (20) | 9/10***,φφ | 8.0 |
| Oseltamivir (40) | Ribavirin (40) | 9/9***,φ,ϕ | |
| Oseltamivir (40) | Ribavirin (20) | 10/10***,φφ,ϕϕ | |
| Oseltamivir (20) | Ribavirin (40) | 10/10***,φ | |
| Oseltamivir (20) | Ribavirin (20) | 9/10***,φ | 10.0 |
| Placebo | 1/20 | 7.2 ± 1.3 |
a
Oral treatments were given twice a day for 5 days starting 4 h prior to virus exposure. *, P < 0.05; **, P < 0.01; ***, P < 0.001, compared to placebo.
b
MDD, mean day of death of mice that died prior to day 21.
c
φ, P < 0.05; φφ, P < 0.01, compared to either compound used alone.
d
ϕ, P < 0.05; ϕϕ, P < 0.01, compared to the sum of survivors from the respective groups treated with monotherapy, indicative of synergy.